Retroviruses

Question 1

Which is the first discovered pathogenic human RT and when was it discovered?

Answer 1

HTLV-1 in 1981

Question 2

When was HIV discovered?

How?

Answer 2

1983
Researchers did extensive interviewing and managed to track it down to a gay male flight attendant working for Air Canada who made frequent trips to France.

Question 3

Describe the genome of HIV

Answer 3

2 strands of +ssRNA
RT
Integrase
Protease
Capsid/matrix proteins (Gag) p24/p17
Envelope proteins (Env)

Question 4

What does the Gag protein encode for?

Answer 4

Matrix, capsid, and nucleo capsid

Question 5

What does the envelope protein encode for?

Answer 5

Glycoprotein

Question 6

What does Pol protein encode for?

Answer 6

Protease, Integrase, and RT

Question 7

How many mistakes does RT make?

Answer 7

1 mistake in about 10,000 nt

Question 8

How can viruses make new types of virions?

Answer 8

Recombination of two viruses or mutants

Question 9

What are the “Five easy steps to retroviral replication”?

Answer 9

1. Retrovirus penetrates host cell
2. After uncoating RTof viral RNA produces dsDNA
3. New DNA tranported to nucleus and integrated as provirus. Provirus may divide indefinitely in host DNA
4. Transcription of provirus may also occur producing RNA for new RT genomes and RNA that codes for RT capsid and envelope proteins.
5. Mature RTvirus leaves host cell by budding

Question 10

How can ARVs inhibit HIV replication?

Answer 10

RT inhibitors
protease inhibitors
fusion/entry inhibitors
integrase inhibitors

Question 11

How does HIV enter the cells?

Answer 11

Env gp 120 connects with CD4 then with coreceptors CXCR4 and CCR5 while HIV gp41 penetrates to begin membrane fusion.

Question 12

How does the RNA get packaged inside the HIV molecule?

Answer 12

gRNA binds to a Gag multimer which binds to the membrane and begins to bud using ESCRT I, III, and ALIX

Question 13

How to RTs spread form cell to cell?

Answer 13

They often do so by cell cell contact through virological synapse or by free virions.

Question 14

How can you tell that a RT is matured?

Answer 14

The core is condensed. The Gag polyprotein needs to be processed by protease to mature. once this happens, they are infectious.

Question 15

Do +ssRNA RT viruses have RdRp in virion?

Answer 15

Yes

Question 16

What is the RT viruses first viral replication step of the genome once in the nucleus?

Answer 16

Reverse transcription

Question 17

Is the HIV RNA infectious on its own?

Answer 17

No

Question 18

At what stage would HIV remain latent?

Answer 18

During integration in the host DNA

Question 19

What diseases does HIV cause?

What diseases does HTLV-1 cause?

Answer 19

AIDS, HAND

ATL, HAM/TSP

Question 20

Left untreated, what does HIV do in terms of damage to the body?

Answer 20

Cardiovascular, liver, kidney, neurological diseases and cancer

Question 21

What are the normal CD4+ T cell counts of a healthy individual?
What are the CD4+ T cell counts that qualify as AIDS?

Answer 21

700-1000 cells/ml

Question 22

What is HBZ? What codes for HBZ?

Answer 22

It inhibits transcription of sense-strand viral RNA and silences integrated proviruses and promotes viral latency.
It is coded by anti-sense transcription of the HTLV-1 genome.

Question 23

How quickly do people succumb from HTLV-1 after diagnosis? How are people diagnosed?

Answer 23

Within 6 months

They are diagnosed by “flower” cancerous T cells

Question 24

What causes HTLV-1 “flower” T cells to form this way?

Answer 24

HBZ and Tax accessory proteins.

Question 25

What are the symptoms of HTLV-1?

Answer 25

Chronic and progressive neurological disease: muscle weakness, arthritis, neurological impairment, urinary incontinence, inflammation of the eye.

Question 26

How do you treat HTLV-1?

Answer 26

Steroids, IFN, ARVs - none successful

Question 27

What does hepadnaviridae family do?

Answer 27

Infect hepatocytes and cause hepatitis

Question 28

Describe the hepatitis B genome

Answer 28

Circular dsDNA
Compact with 4 overlapping ORFs
No untranscribed regions
hepatocyte specific enhancer sequence

Question 29

Describe HBV’s viral envelope

Answer 29

hepatocyte surface proteins

3 viral envelope proteins, S, M, and L

Question 30

How does HBV enter host cell?

Answer 30

Uses pre S env protein to endocytose binding to heparin sulfate

Question 31

What is cccDNA?

Answer 31

covalently closed circular DNA that HBV forms after binding to histones in host nucleus

Question 32

What is HBV P protein?

What does it need to activate?

Answer 32

An RT - It binds to Epsilon the encapsidation signal

Requries Hsp90 and p23

Question 33

Why does HBV produce so many extra capsids?

Answer 33

To confuse the immune system

Question 34

What is HBV HBx? What is it’s function?

Answer 34

An accessory protein that is a weak transcription factor and appears to interfere with host immune responses. Down regulates the proteasome.
Can block p53 which is an anti-tumour protein so therefore blocks apoptosis and causes cancer.

Question 35

Who is the most at risk for HBV? Why?

Answer 35

Newborns because chronic hepatitis correlates with inverse age of infection

Question 36

How does the immune system act in HBV?

Answer 36

CD8 cells induce apoptosis of hepatocytes and produce cytokines which attract neutrophils and monocytes which cause most of the damage.

Question 37

What is the best therapy for HBV?

What does this do?

Answer 37

IFN gamma therapy

Upregulates proteasomes and inactivates HBx

Question 38

Describe the HBV vaccine.

Answer 38

subunit vaccine base on S gene which expresses S, M, and L proteins. Used to make VLP in yeast. Also live attenuated but dangerous.

Question 39

What populations are at risk for HBV?

Answer 39

Newborns
Health workers
IV drug users
Ppl with multiple sex partners

Question 40

Hepatitis is a(n) ______ mediated disease.

Answer 40

Immune